Ribaxamase, an orally administered β-lactamase, protects the gut microbiome in patients treated with ceftriaxone (original) (raw)

Ribaxamase is an orally delivered β-lactamase intended to be co-administered with intravenous β-lactam antibiotics (penicillins and cephalosporins) to protect the gut microbiome from excess antibiotics excreted into the gastrointestinal tract. In a placebo-controlled, multinational Phase 2b proof-of-concept clinical study, ribaxamase significantly reduced the incidence of Clostridium difficile infection in patients treated with ceftriaxone for a lower respiratory tract infection. Patients could also receive treatment with macrolides at the discretion of the clinician. During the clinical study, three sequential fecal samples were collected for analysis of the gut microbiome and microbiologic determination of intestinal colonization by certain pathogens. Changes in the gut microbiome were analyzed using 16S rRNA gene sequencing. Ribaxamase significantly ameliorated the loss of alpha and beta diversity as compared with the placebo group. During the clinical study, significantly more placebo patients became newly colonized with vancomycin resistant enterococci (VRE), and the present microbiome analysis determined that significantly more placebo patients also became monodominated by enterococci (15 vs. 4). Notably, VRE-colonized patients had a significant reduction in gut microbiome alpha diversity as compared with non-colonized patients. These data demonstrate that ribaxamase limited antibiotic-mediated damage to the gut microbiome in patients treated with ceftriaxone and support further clinical development. Ribaxamase is a unique gut microbiome protectant intended to reduce opportunistic infections like C. difficile in patients receiving IV β-lactam antibiotics. Kokai-Kun JF (2019) Ribaxamase, an orally administered β-lactamase, protects the gut microbiome in patients treated with ceftriaxone